Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics Laboratory, |
RCV001173916 | SCV001337034 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV001229968 | SCV001402432 | pathogenic | Charcot-Marie-Tooth disease, type I | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 157 of the PMP22 protein (p.Arg157Trp). This variant is present in population databases (rs28936682, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal recessive Dejerine-Sottas disease (PMID: 10211478, 32719652). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8444). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PMP22 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001332355 | SCV001524655 | likely pathogenic | Hereditary liability to pressure palsies | 2020-08-04 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Illumina Laboratory Services, |
RCV001229968 | SCV005431536 | pathogenic | Charcot-Marie-Tooth disease, type I | 2024-11-22 | criteria provided, single submitter | clinical testing | The PMP22 c.469C>T p.(Arg157Trp) missense variant has been identified in trans with a pathogenic variant in individuals with a phenotype consistent with Charcot-Marie-Tooth disease. This variant has been shown to segregate with disease (PMID: 10211478; 32719652). This variant is not observed at a significant frequency in version 4.1.0 of the Genome Aggregation Database. Multiple lines of computational evidence suggest the variant may impact the gene or gene product. This variant has been classified as likely pathogenic or pathogenic by multiple submitters in ClinVar. Based on the evidence, the c.469C>T p.(Arg157Trp) variant has been classified as pathogenic for Charcot-Marie-Tooth disease. |
| OMIM | RCV000008957 | SCV000029169 | pathogenic | Autosomal recessive Dejerine-Sottas syndrome | 1999-04-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000193053 | SCV000243949 | not provided | Charcot-Marie-Tooth disease type 1E | no assertion provided | literature only |